Cyclic amino acids of general Formula I:
wherein R1 is H or a lower alkyl radical and n is 4, 5, or 6, are known to be useful in the treatment of certain cerebral and neurodegenerative diseases. See, e.g., U.S. Pat. Nos. 4,087,544 and 5,084,479, which are incorporated herein by reference in their entireties. For example, when R1 is hydrogen and n is 5, the cyclic amino acid is 1-(aminomethyl)-1-cyclohexaneacetic acid, which is also known as gabapentin. Gabpentin has been shown to be useful as an anticonvulsant agent.
However, the use of such cyclic amino acids in the preparation of medicaments has been limited because such cyclic amino acids easily degrade during storage. The degradable is believed to be due, at least in part, to conversion of the cyclic amino acid to its lactam of Formula II:

The lactams of Formula II are particularly undesirable in the preparation of medicaments because of their relatively high toxicities, as compared to the cyclic amino acids of Formula I. To reduce the concentration of lactam, the cyclic amino acids of Formula I are typically treated with a mineral acid, for example hydrochloric acid. For example, when gabapentin is treated with a semi-concentrated solution of hydrochloric acid (HCl), the lactam is hydrolyzed and converted back to the pure gabapentin form. In other words, the treatment with HCl constitutes a purification process of gabapentin necessary to eliminate the lactam impurity.
However, the purification of cyclic amino acids of Formula I with a mineral acid leaves residual mineral acid anions in contact with the purified cyclic amino acid. Although the mineral acid is needed to convert the lactam to its cyclic amino acid form, the continued presence of the mineral acid anions causes the purified cyclic amino acid to form its corresponding lactam upon storage. Without being bound by theory, it is believed that the highly ionizable, electronegative mineral acid anion, being in close proximity to the cyclic amino acid and surrounded by the surfaces of compressed powder excipients (which are typically used in the preparation of medicaments), displays the tendency to attract water in the form of hydronium ions (H3O+) in order to remain coupled in its thermodynamically stable state, e.g., (H3O+)(Cl−). Re-cyclization of the cyclic amino acid to form the lactam impurity provides the water molecules necessary for creation of the thermodynamically stable state described above.
In the past, the rate at which the purified cyclic amino acid degrades to form the lactam impurity was decelerated by carefully controlling the amount of residual mineral acid anions present. For example, U.S. Pat. No. 6,054,482 (the 482 patent), which is incorporated herein by reference in its entirety, describes a pharmaceutical composition containing: i) an active ingredient such as gabapentin in the free amino acid, crystalline anhydrous form containing less than 0.5% by weight of its corresponding lactam and less than 20 ppm of an anion of a mineral acid, and ii) one or more pharmaceutically acceptable adjuvants that do not promote conversion of more than 0.2% by weight of the gabapentin to its corresponding lactam form when stored at 25° C. and an atmospheric humidity of 50% for one year. However, controlling the amount of residual mineral acid anion is both expensive and time consuming. The '482 patent also discloses the use of certain, inert powder excipients to further stabilize the amino acid with respect to its lactam. However, it is known that the use of the disclosed excipients in formulations having 20 ppm or more of the mineral acid anion do not provide acceptably stable solid dosage forms of the amino acid. Hence, compositions and methods which address these needs have long been sought.